Present evidence suggests that proteolytic enzyme induced emphysema in animals is caused by elastolysis of lung elastic tissue. The resulting experimental lesion most closely resembles human panlobular emphysema. If the production of this emphysema is caused by elastolysis of lung elastin, then studies on the chemistry of this reaction might be facilitated by examining many of the properties of the in vitro elastase-elastin system. By chemical modification of elastase, it is possible to obtain various preparations of the enzyme which have altered elastolytic activity, but little or no change in their ability to cleave small soluble peptides. The endotracheal instillation in hamsters of these various enzyme preparations will allow us to gain greater insight into the mechanism of enzyme-induced emphysema. A direct relationship between the severity of emphysema induced in vivo and the ability of these elastase preparations to solubilize elastin in vitro would be striking evidence for the elastolytic hypothesis of experimental emphysema. If lung elastin is the initial site of action for the production of emphysema, it may be possible to modify the course of the disease by the use of chemical agents which are known to inhibit or stimulate elastolysis in vitro. The site of elastolytic activity in the lung and the turnover of administered elastase in the lung will be determined by the use of radioactive enzyme.